Fezolinetant treatment of moderate-to-severe vasomotor symptoms due to menopause: effect of intrinsic and extrinsic factors in two phase 3 studies (SKYLIGHT 1 and 2).

OBJECTIVE: This study aimed to assess the efficacy of the neurokinin 3 receptor antagonist, fezolinetant, according to several intrinsic (individual related) and extrinsic (external influence) factors that may influence the frequency and severity of moderate-to-severe vasomotor symptoms (VMS) using pooled 12-week data from SKYLIGHT 1 and 2. METHODS: SKYLIGHT 1 and 2 were two phase 3, randomized, double-blind studies conducted from July 2019 to August 2021 (SKYLIGHT 1) or April 2021 (SKYLIGHT 2). Participants were initially randomized to receive daily doses of placebo, fezolinetant 30 mg, or fezolinetant 45 mg. After 12 weeks, placebo participants were rerandomized to receive fezolinetant 30 mg or 45 mg, whereas those receiving fezolinetant continued on the same dose. Change in VMS frequency from baseline to week 12 was used to assess efficacy according to several intrinsic and extrinsic factors. Overall efficacy and safety were also investigated. RESULTS: Overall, 1,022 individuals were included. Fezolinetant was efficacious in reducing VMS frequency across all intrinsic and extrinsic factors. Efficacy was most notable for participants who self-identify as Black (least squares mean difference for fezolinetant 45 mg versus placebo, -3.67; 95% CI, -5.32 to -2.01), current smokers (-3.48; -5.19 to -1.77), and current alcohol users (-3.48; -4.42 to -2.54). Overall efficacy was -2.51 (95% CI, -3.20 to -1.82) for fezolinetant 45 mg versus placebo. Similar findings were observed for the fezolinetant 30 mg dose. Comparable incidences of treatment-emergent adverse events were observed for placebo (132 of 342 individuals [38.6%]), fezolinetant 30 mg (132 of 340 individuals [38.8%]), and fezolinetant 45 mg (135 of 340 individuals [39.7%]). CONCLUSIONS: None of the intrinsic and extrinsic factors analyzed substantially reduced the efficacy response to fezolinetant in SKYLIGHT 1 and 2. These data provide additional confidence for using fezolinetant in a diverse population of individuals with VMS.

Assessment of women's treatment preferences for vasomotor symptoms due to menopause.

BACKGROUND: Several therapies for vasomotor symptoms (VMS) due to menopause are available. Treatment preferences and willingness-to-pay for VMS treatment among US women with VMS were evaluated. METHODS: An online survey of women with perimenopausal or postmenopausal VMS was conducted (3/15/21-4/23/21). A discrete choice experiment quantified the impact of 7 treatment attributes on VMS treatment choice: VMS frequency/severity reduction, sleep improvement, risk of breast cancer/cardiovascular events in 6 years, risk of short-term side effects, and out-of-pocket costs. Preference weights (PWs) with 95% confidence intervals (CIs) were estimated and reported. RESULTS: Among 467 women, 86.5% and 87.8% reported moderate to very severe VMS and sleep problems during the preceding month, respectively. Sleep improvement (PW: 0.843; 95% CI: 0.721, 0.965) and reduction in VMS frequency (PW: 0.658; 95% CI: 0.520, 0.796) and severity (PW: 0.628; 95% CI: 0.500, 0.756) most influenced treatment preference; risk of cardiovascular events (PW: 0.150; 95% CI: 0.069, 0.232) or breast cancer (PW: 0.401; 95% CI: 0.306, 0.496) in 6 years had lesser effect. Willingness-to-pay was an additional $35-$46/month for substantially improved sleep, 80% VMS frequency reduction, and reduction from severe to mild VMS. CONCLUSIONS: Sleep improvement and reductions in VMS frequency/severity were the most important treatment attributes.

Hormone and non-hormone treatments are available to reduce vasomotor symptoms (hot flashes and night sweats) due to menopause. We conducted an online survey of 467 women with moderate to very severe vasomotor symptoms during perimenopause or postmenopause to learn what treatment attributes are most important to women when selecting from among the available therapies and how much women were willing to pay for the attributes. Women were shown 14 cards, each with a side-by-side comparison of 2 treatments with varying descriptions of the following 7 treatment attributes: reduction in frequency of vasomotor symptoms, reduction in severity of vasomotor symptoms, improvement in sleep, risk of breast cancer in 6 years, risk of cardiovascular events in 6 years, risk of short-term side effects, and out-of-pocket costs. Women picked their preferred treatment on each card. Results showed that improvement in sleep was the most important attribute to women, and they were willing to pay an extra $46/month for a treatment that substantially improved sleep. The next most important attributes were reduction in frequency and reduction in severity of vasomotor symptoms. Women were willing to pay $36/month more for a treatment that reduced symptom frequency by 80% compared with one that reduced frequency by 50%, and they were willing to pay $35/month more for treatment that reduced symptoms from severe to mild compared with one that did not reduce symptom severity. These results may help guide development of new treatment options and may help physicians recommend treatments that best fit women's preferences.

Practice patterns and perspectives regarding treatment for symptoms of menopause: qualitative interviews with US health care providers.

OBJECTIVE: To document health care providers' views regarding treatments for symptoms associated with menopause and discussions with patients about symptoms and treatment decisions. Results informed development of a data collection form for a retrospective medical record review (reported separately). METHODS: Registered US gynecologists or primary care providers from all US regions were identified from local association directories and an in-house database and were invited to participate in a qualitative interview if they consulted with three or more patients per week presenting with menopausal symptoms. Participants provided demographic data, information about patients' symptoms, and health care provider and patient views on prescription and nonprescription therapies. Key concepts/themes from interviews were identified. RESULTS: Participating health care providers (10 gynecologists, 10 primary care providers) agreed there are effective treatment options for menopausal symptoms, particularly vasomotor symptoms and vaginal dryness and/or atrophy. Health care providers reported that treatment was generally dictated by symptoms that interfered with quality of life and/or daily activities, although patients often had symptoms for months before presentation. All health care providers said they prescribe hormone and/or nonhormone therapies for treatment of menopausal symptoms; half stated that they typically inquire about patients' nonprescription therapy use, and 45% recommend specific nonprescription therapies. The most commonly cited barriers to initiation of any therapy for menopausal symptoms were patient concerns about risks and financial considerations (ie, insurance or cost). CONCLUSIONS: US health care providers reported prescribing therapies for menopausal symptoms and noted that these therapies were perceived as generally effective; however, barriers to initiation of prescription therapy exist, and new treatment options are needed.

Treatment and resource utilization for menopausal symptoms in the United States: a retrospective review of real-world evidence from US electronic health records.

OBJECTIVE: The aim of this study was to generate real-world evidence documenting use of prescription and nonprescription therapies recorded by health care providers for women experiencing vasomotor symptoms (VMS) associated with menopause. METHODS: This noninterventional, retrospective, observational cohort study used data from US patient medical records. Participating health care providers were gynecologists, internal medicine/family physicians, or advanced practice providers who typically saw three or more women per week presenting with menopausal symptoms and could identify eligible medical records; providers were recruited from local medical association directories and from listings from previously conducted research. Eligible women presented January 2016 through December 2019, were 40 to 60 years of age, and reported experiencing bothersome hot flashes at least twice within 24 hours. RESULTS: A total of 283 health care providers provided data for 1,016 women. The most common symptoms at initial presentation were hot flashes (91.2%), sleep problems (49.9%), and vaginal dryness (47.0%). At least one therapy for menopausal symptoms was recorded for 883 women (86.9%), and 611 (60.1%) had documentation of prescription medication, most commonly hormone therapy (70.4%). Nearly 40% of women had no prescription medication documented, and approximately 13% had no therapy documented. Despite experiencing bothersome menopausal symptoms, approximately 50% delayed seeking care for more than 6 months. Women had a mean of 2.1 (SD, 2.0) office visits related to menopause from initial presentation to completion of review, and health care resource utilization did not vary by treatment status. Subgroup analyses indicated nominal differences in treatment use across ethnic groups and varying prescribing patterns for menopausal symptoms by practitioner type and US region. CONCLUSIONS: A high proportion of women with VMS remain untreated even when experiencing bothersome symptoms of menopause. Improved management of VMS is required to provide relief from the symptoms effectively and safely.

Understanding Attitudes, Beliefs, and Behaviors Surrounding Menopause Transition: Results from Three Surveys.

Purpose: To understand women's perspectives, attitudes, and beliefs surrounding menopause transition and increase understanding of digital technology use for symptom management. Patients and Methods: Information was obtained using three studies of women aged 40-65 years experiencing menopause transition symptoms. The HealthyWomen online cross-sectional survey was designed to reflect an inclusive sociodemographic sample representative of the US population. BECOME was a blinded, ethnographic, qualitative research study of women's menopause transition experiences and comprised facilitator-led online asynchronous discussions, online homework entries, and audio-only teleconferences. The NODE.Health online, two-part, cross-sectional patient survey was designed to capture patient and healthcare provider (HCP) sentiment about the use of digital health technologies to address gaps in perimenopausal symptom knowledge and management. Results: The HealthyWomen survey included 1045 participants, 37 were included in BECOME, and 100 completed the NODE.Health survey. Hot flashes, night sweats, and sleep problems were the most frequently experienced symptoms in the HealthyWomen survey, and over half of participants experiencing symptoms felt the need to seek relief. Whether menopause was considered a medical problem or natural process differed by self-identified race, culture, and ethnicity, as did the likelihood of consulting a HCP over symptoms. Participants preferred to discuss menopause transition with HCPs who did not rush them, were good listeners, and had expertise in the area. Most technology experience was with health websites, but nearly half were unsatisfied with online resources describing menopause-related symptoms. Convenience, ease of use, and accessibility were the most common reasons for pursuing digital health technology. Conclusion: Factors such as cultural beliefs, values and attitudes towards menopause determine personal experiences. More open discussions with friends, family, and HCPs may raise awareness and reduce barriers to seeking help. To provide optimal care throughout the menopause transition, HCPs should consider patients' psychosocial and cultural backgrounds, and personal and subjective perspectives.